The current invention pertains to a device for the analysis of coagulation and/or aggregation reaction of blood.
Such devices are already known. For example DE 32 47 815 A1 describes a device for the measurement of the bleeding time in vitro, where the blood is fed under constant pressure gradient through an opening, whereas it is provided with a device for the direct or indirect measurement of the resulting blood stream. One side of the opening is made of a porous material, which is preferably a filtering material, which shows a pore size in a range between 0.01 and 5 μm. This piece is mounted in a case in such a way that the blood extracted from a supply container and fed over a capillary of the opening is mainly flowing through the opening and no blood is running past the side of the piece.
From this prior art it is also known that the material of the piece contained in this opening is saturated with a solution which will aggregate or coagulate the blood platelets of the blood, before starting the analysis, preferably in adenosine diphosphate (ADP). Also known from this prior art is that the material of the piece contained in the opening is coated with collagen.
By soaking the porous piece with adenosine phosphate or with other substances, the bleeding rates can be imitated with even more precise in vivo conditions, because during a real injury, the injured vessel wall releases adenosine phosphate, thereby inducing the platelets aggregation.
By coating the filtering fibres of the porous piece with collagen, we obtain a better repeatability and a shorter bleeding time, because the filtering fibres coated with collagen from the porous piece in the border area of the opening favor the adhesion of the blood platelets.
It is also known since 1965 how to produce single use pieces for measuring the bleeding time in vitro (Thrombostat 4000, producer: VDG of Goltz GmbH, 83370 Seeon). These single use pieces consisted of a porous material with an opening with a diameter of 150-120 μm and were coated with collagen fibres dispersed in solution and then dried, in order to extend the durability. This is described in detail in U.S. Pat. No. 5,854,076 (column 2, paragraph 1). The single use parts were stored in bags with a drying material, until they were used for measurements in patients. In order to perform the measurement, the dried collagen was supposed to be reconstituted by adding a liquid, so that the collagen fibres were transferred again in the initial hydrated state. In addition, platelets aggregating substances, like for example ADP or CaCl2, could be added, as described in the article “In vitro bleeding test—a simple method for the detection of aspirin effects on platelet function”, by Kretschner V, Schikor B., Sohngen D Dietrich G., Thromb. Res., 1989 Dec. 1; 56 (5), pages 593-602.
From EP D 716 744 B1 we also know of a porous separating element which shows an opening that has at least one substance built-in and dried, which at the time of measurement, when blood is streaming through the opening, can be reconstituted, in order to initiate the blood coagulation process or the thrombocyte aggregation in the blood. The substances used to initiate the blood coagulation are either ADP, ristocetine, arachidonic acid, thrombin, epinephrine, thrombocyte activation factor (PAF) or thrombin-receptor-agonist-peptide (TBAP). Furthermore, the porous separating element can contain collagen, which also induces the aggregation of the blood platelets.
A problem of the known addition of adenosine phosphate (ADP) together with collagen consists in the fact that ADP is degraded through polluted ADPases to adenosine, which inhibits the formation of platelets. This is the reason why the ADP concentration must be relatively high, in order to achieve the desired reaction.